The effects produced by the release of a neurotransmitter may not always be straight-forward since many agents may interact to modulate synaptic activity. One group of possible neuromodulators are peripheral hormones, which reach the brain via the circulatory system. For example, considerable research suggests that gonadal steroids interact with hypothalamic catecholamine (CA) neurons. Although less abundant, there is also evidence that gonadal steroids modulate striatal CA activity. In preliminary studies we have shown that gonadal steroids modulate amphetamine (AMPH)-stimulated release of CA from striatal tissue fragments in vitro. In addition, we have described sex and estrous cycle-related differences in AMPH-elicited rotational behavior, which were related to sex differences in the lateralization of striatal dopamine (DA). Both in vitro and in vivo experiments are proposed here to further elucidate 1) the extent of sex differences in striatal asymmetry, function and neurochemistry, and 2) the role of the gonadal hormones in modifying striatal activity. The experiments involve using AMPH-elicited rotational behavior as an index of nigrostrital activity. Behavior will be related to striatal CA content, the asymmetrical release of CA in vitro and striatal DA receptor-binding. In addition, the role of sex differences in AMPH-elicited behaviors will be assessed. These experiments will establish that hormones play a broader role in brain function than previously believed, and will provide a first step in understanding sex and estrous cycle-related differences in behavior. The experiments also have implications for a variety of human disorders which may involve dysfunction of brain CA.